Knowingthestructure,dynamicsandligandbindingspecificityofproteinsandnucleicacidsisessentialto understandingthemechanismsofhumandiseaseandtotheoptimaldesignofmoleculesthatcanintervene therapeuticallyindiseaseprocesses.NuclearMagneticResonance(NMR)Spectroscopyisoneofthemost versatiletechniquesforobtainingthismolecularinformation.ThistremendousvalueofNMRinbiomedical scienceisonlyrealizedthroughtheapplicationofpowerfulcomputationaltools.Ourgoalinthisprojectisto extendandhardenthreeexistingsoftwareprogramsforthecomputationalanalysisofNMRdataintoa powerful,butuser-friendly,integratedsuite.HavingeffectivesoftwareforNMR,asweareproposing,is especiallycriticalaswerealizethatthedeepinsightintomacromolecularstructureandfunctioncomesnot fromasingletechniquelikeNMR,butfromthecomplementaryinformationfromvarioustechniquesincluding NMR,X-raycrystallography,andCryo-electronmicroscopy.Scientistsarenolongerseeingthesetechniques asspecializedtechniquesusablebyonlydomainexperts,butasacollectionoftechniquesthatcanandshould beappliedtogether.DespitethisessentialroleforNMRandthekeyneedforaccessiblecomputationaltoolsin itsuse,theredoesnotexistanintegratedsoftwareenvironmentthatspansthemajorstepsofmacromolecular NMRanalysis.Researchersmustuseavarietyoftoolsfromdifferentlabsthathavedifferentprogramming languages,scriptingtools,namingconventions,graphicalinterfaces,documentationstylesetc.Theproject proposedhereaimstoresolvethisimportantissuebythefurtherdevelopmentandhardeningofthreeexisting softwareapplications,allpreviouslydevelopedbythePI,intoanintegratedsoftwaresuite,NMRFx.NMRFx ProcessorwillprovidethesignalprocessingnecessarytotransformNMRdataintousablespectra.NMRFx ViewerwillprovideadvancedtoolsforvisualizingandanalyzingtheNMRspectra.NMRFxStructurewillallow calculatingmacromolecularstructuresconsistentwiththedata,andcalculatingstructuredependentNMR propertiessuchaschemicalshifts.Integratingthetoolswillnotonlymaketheirusemoreaccessibleand efficient,buttightintegrationwillallownewapproachestocomputationalanalysisthatmoveawayfromthe traditionallinearsequenceofstepsintoamoreholisticapproachtoextractinginformationfromthedata. Developmentoftheintegratedsoftwareplatformproposedherewillsubstantiallylowerthebarrierandbetter supportnewusersinaccessingtheimportantinformationthatNMRcanprovide.Weproposethatbyproviding new,andevenexperiencedusers,withasoftwaretoolsetthathasacommoninstallationprotocol,interface style,datastructures,andoveralldesign,wecansubstantiallylowerthesebarrierstouse.Doingthiswill maketheuseofNMRtechniquesmoreaccessibletoawiderpopulationofresearchersandincreasetheuse ofNMRinabroadrangeofbiologicalresearchareasthatimpactonhumanhealth.